Support is requested for a Keystone Symposia meeting entitled PI 3-Kinase and Interplay with Other Signaling Pathways, organized by Christian Rommel, Kevan M. Shokat and Jose Baselga. The meeting will be held in Keystone, Colorado from February 24 - March 1, 2013. How metabolic pathways are regulated to meet the unique needs of tumor cells is not well understood, but mounting evidence suggests that metabolic regulation in cancer cells is intimately linked with the signal transduction pathways that control cell growth and proliferation. The PI3K-Akt-mTOR signaling pathway is one of the primary mechanisms for controlling tumor cell growth, survival, and motility in response to oncogenic signaling and extracellular cues. Genetic events resulting in inappropriate activation of this pathway are common in many cancers and, as a result, are a focus of both basic cancer research and drug discovery efforts in oncology. Although originally modeled as an independent and linear signaling cascade, today it is evident that the PI3K pathway also functions as a central hub for cross-talk in both vertical as well as reciprocal feedback regulation with other important signaling pathways. One of the most exciting advances in the field is the development of new inhibitors against this pathway. However, the rationale for inhibiting individual or multipl isoforms of PI3K/Akt/mTOR signaling remains a subject of intense debate. This meeting aims to bring together scientists and clinicians from academia and industry to discuss the opportunities and liabilities of targeting the PI3K- and related pathways in disease, drawing on human pathophysiology and genetics, preclinical models and clinical data with PI3K pathway inhibitors. A joint meeting addressing Tumor Metabolism will enhance opportunities for interdisciplinary interactions.